Sanders was born in Saint Petersburg, Russian Empire, at number 6 Petrovski Ostrov. His parents were Henry Peter Ernest Sanders [1](1868–1960),[2] and Margarethe Jenny Bertha Sanders (1883–1967) née Kolbe, born in Saint Petersburg, of mostly German, but also Estonian and Scottish ancestry.[3][4] A biography published in 1990 claimed that Sanders's father was the illegitimate son of a Russian noblewoman of the Czar’s court and a prince of the House of Oldenburg, married to a sister of the Czar.[5]a[›] The actor Tom Conway (1904–1967) was George Sanders's elder brother. Their younger sister, Margaret Sanders, was born in 1912.

Sanders made his British film debut in 1929. Seven years later, after a series of British films, he took his first role in an American production in Lloyd's of London (1936) as Lord Everett Stacy. His smooth upper-class English accent, his sleek manner and his suave, superior and somewhat threatening air made him in demand for American films for years to come.[9] He gravitated to supporting roles in A-pictures, often with all-British casts, such as Alfred Hitchcock's Rebecca (1940), in which he and Judith Anderson played cruel foils to Joan Fontaine's character, and in the same director's Foreign Correspondent, later that year, where he played one of his few heroic parts in a Europe threatened by Fascism.

His early leading roles were in B-pictures and adventure serials; in his first American job as a leading man, the rarely-seen International Settlement, (1938) with Dolores Del Rio he rose above material to play a sophisticated British man of danger; it did so well that it led to the title role in two popular wartime film series with similar characters, one based on The Falcon and the other on The Saint.[10] He played a smooth American Nazi in Confessions of a Nazi Spy (1939) with Edward G. Robinson. Rage in Heaven (1941), an early film noir, cast him as the trustworthy good guy whose best friend, Robert Montgomery, goes murderously insane and sets him up for the rap, but such forays were seldom. By 1942, Sanders handed the role of the Falcon to his brother Tom, in The Falcon's Brother. The only other film in which the two acting siblings appeared together was Death of a Scoundrel (1956), in which they also played brothers.

Two ghostwritten crime novels were published under his name to cash in on his fame at the height of his wartime film series. The first was Crime on My Hands (1944), written in the first person, and mentioning his Saint and Falcon films. This was followed by Stranger at Home in 1946. Both were actually written by female authors: the former was by Craig Rice, and the latter by Leigh Brackett.

In 1958 Sanders recorded an album called The George Sanders Touch: Songs for the Lovely Lady. The album, released by ABC-Paramount Records, featured lush string arrangements of romantic ballads, crooned by Sanders in a fit baritone/bass (spanning from low to middle C), including "Such is My Love", a song he had himself composed. After going to great lengths to get the role he appeared in the Broadway cast of South Pacific, but was overwhelmed with anxiety over the singing and quickly dropped out. His singing voice can be heard in Call Me Madam (1953). He also signed on for the role of Sheridan Whiteside in the stage musical Sherry! (1967), based on Kaufman and Hart's play The Man Who Came to Dinner, but he found the stage production demanding and quit after his wife Benita Hume discovered that she had terminal bone cancer.

On 27 October 1940 Sanders married Susan Larson. The couple divorced in 1949. From later that year until 1954 Sanders was married to Zsa Zsa Gabor, with whom he starred in the film Death of a Scoundrel (1956) after their divorce. On 10 February 1959 Sanders married Benita Hume, widow of Ronald Colman. She died in 1967, the same year Sanders's brother Tom Conway died of liver failure. Sanders had become distant from his brother because of Conway's drinking problem.[14] Sanders endured a further blow in the same year with the death of their mother, Margarethe.

Sanders's autobiography, Memoirs of a Professional Cad, was published in 1960 and gathered critical praise for its wit. Sanders suggested the title A Dreadful Man for his biography, which was later written by his friend Brian Aherne and published in 1979.[15]

Sanders's last marriage, on 4 December 1970, was to Magda Gabor, the elder sister of his second wife. This marriage lasted only 32 days, after which he began drinking heavily.[16]

Sanders suffered from dementia, worsened by waning health, and visibly teetered in his last films, owing to a loss of balance. According to Aherne's biography, he also had a minor stroke. Sanders could not bear the prospect of losing his health or needing help to carry out everyday tasks, and became deeply depressed. At about this time he found that he could no longer play his grand piano, so he dragged it outside and smashed it with an axe. His last girlfriend persuaded him to sell his beloved house in Majorca, Spain, which he later bitterly regretted. From then on he drifted.[17]

On 23 April 1972, Sanders checked into a hotel in Castelldefels, a coastal town near Barcelona. He was found dead two days later, having gone into cardiac arrest after swallowing the contents of five bottles of the barbiturate Nembutal.[18][19] He left behind three suicide notes, one of which read:

Dear World, I am leaving because I am bored. I feel I have lived long enough. I am leaving you with your worries in this sweet cesspool. Good luck.[20][21][22]

His signature appeared under the message.

Sanders's body was returned to Britain for funeral services, after which it was cremated and the ashes were scattered in the English Channel.

David Niven wrote in Bring on the Empty Horses (1975), the second volume of his memoirs, that in 1937 his friend George Sanders had predicted that he would commit suicide when he was 65, and that in his 50s he had appeared to be depressed since his marriages had failed and several tragedies had befallen him.[23]